血浆 NfL 和 p-tau181 对帕金森病认知障碍的可分离贡献。

Dissociable contribution of plasma NfL and p-tau181 to cognitive impairment in Parkinson's disease.

机构信息

Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain; Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain; Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain.

Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain; Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain.

出版信息

Parkinsonism Relat Disord. 2022 Dec;105:132-138. doi: 10.1016/j.parkreldis.2022.05.020. Epub 2022 Jun 8.

DOI:10.1016/j.parkreldis.2022.05.020

PMID:35752549

Abstract

BACKGROUND

Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofilament light chain (NfL), a marker of neuronal injury, has shown good performance for PD disease stratification and progression. While NfL is not disease-specific, phosphorylated-tau at threonine-181 (p-tau181) in blood is a highly specific marker of concomitant brain amyloid-β and tau pathology.

METHODS

We investigated the potential of plasma NfL and p-tau181 levels as markers of cognitive impairment in a prospective cohort of 109 PD patients with and without PD-MCI (age 68.1 ± 7 years, education 12.2± 5 years), and 40 comparable healthy controls. After a follow-up of 4 years, we evaluated their predictive value for progression to dementia.

RESULTS

Although NfL and p-tau181 levels were significantly increased in PD compared with healthy controls, only NfL levels were significantly higher in PD-MCI compared with PD with normal cognition (PD-NC) at baseline. After a follow-up of 4 years, only NfL predicted progression to dementia (HR 1.23, 95% CI 1.02-1.53; p = 0.038). Significant correlations between fluid biomarkers and neuropsychological examination were only found with NfL levels.

CONCLUSIONS

Plasma NfL levels objectively differentiates PD-MCI from PD-NC patients, and may serve as a plasma biomarker for predicting progression to dementia in PD. Plasma levels of p-tau181 does not seem to help in differentiating PD-MCI or to predict future cognitive deterioration.

摘要

背景

认知功能障碍是帕金森病（PD）的一种致残并发症。PD 轻度认知障碍（PD-MCI）的诊断准确性取决于所进行的测试，这限制了结果的推广。基于血液的生物标志物可为 PD-MCI 诊断和进展提供额外的客观信息。血液神经丝轻链（NfL）是神经元损伤的标志物，已显示出对 PD 疾病分层和进展的良好性能。虽然 NfL 不是疾病特异性的，但血液中的磷酸化 tau 丝氨酸 181（p-tau181）是同时存在的脑淀粉样β和 tau 病理学的高度特异性标志物。

方法

我们在一个前瞻性队列中研究了血浆 NfL 和 p-tau181 水平作为 109 例 PD 患者（年龄 68.1±7 岁，教育程度 12.2±5 年）和 40 例可比健康对照者认知障碍的标志物的潜力，这些患者中有 PD-MCI（年龄 68.1±7 岁，教育程度 12.2±5 年）和无 PD-MCI（PD-NC）。经过 4 年的随访，我们评估了它们向痴呆进展的预测价值。

结果

尽管与健康对照组相比，PD 患者的 NfL 和 p-tau181 水平明显升高，但仅在 PD-MCI 患者中，NfL 水平明显高于 PD-NC 患者。经过 4 年的随访，只有 NfL 预测向痴呆进展（HR 1.23，95%CI 1.02-1.53；p=0.038）。只有 NfL 水平与神经心理学检查之间存在显著相关性。